広島大学

Basic Information

Major Professional Backgrounds

• 2020/04/01, 2020/06/30, Center For Integrated Medical Research, Hiroshima University Hospital, Assistant Professor
• 2020/07/01, 2021/03/31, Clinical Research Center in Hiroshima, Hiroshima University Hospital, Assistant Professor
• 2021/04/01, 2023/03/31, Ministory of Health, Labour and Welfare Goverment of Japan, Office of Medical Devices Policy, Health Policy Bureau, Officer
• 2023/04/01, 2024/03/31, Ministry of Health, Labour and Welfare Goverment of Japan, Office of Medical Devices Policy, Policy Planning Division for Pharmaceutical Indusry Promotion and Medical Information Management, Health Policy Breau, Unit Chief
• 2024/04/01, Clinical Research Center in Hiroshima, Hiroshima University Hospital, Assistant Professor

Research Fields

• Medicine,dentistry, and pharmacy;Society medicine;Medical and hospital management
• Medicine,dentistry, and pharmacy;Basic medicine;Pathological medical chemistry
• Biological Sciences;Oncology;Tumor therapeutics
• Medicine,dentistry, and pharmacy;Pharmacy;Biological pharmacy

Research Keywords

• integrin, extracellular matrix, cancer biology, Myc, senescence, neuroblastoma, glioblastoma, regenerative medicine

Affiliated Academic Societies

• The Pharmaceutical Society of Japan
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• The Japanese Association for Molecular Target Therapy of Cancer
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Research Activities

Academic Papers

1. The Promoting Effect of the Extracellular Matrix Peptide TNIIIA2 Derived from Tenascin-C in Colon Cancer Cell Infiltration, International Journal of Molecular Sciences, 20170117
   Link to Paper Search Results by DOI
2. Combining peptide TNIIIA2 with all- trans retinoic acid accelerates N-Myc protein degradation and neuronal differentiation in MYCN-amplified neuroblastoma cells, American Journal of Cancer Research, 20190201
3. Peptide TNIIIA2 Derived from Tenascin-C Contributes to Malignant Progression in Colitis-Associated Colorectal Cancer via beta1-Integrin Activation in Fibroblasts, International Journal of Molecular Sciences, 20190605
   Link to Paper Search Results by DOI
4. Autocrine Production of PDGF Stimulated by the Tenascin-C-Derived Peptide TNIIIA2 Induces Hyper-Proliferation in Glioblastoma Cells, International Journal of Molecular Sciences, 20190628
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5. ★, Inactivation of beta1 integrin induces proteasomal degradation of Myc oncoproteins, Oncotarget, 20190813
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6. ★, Aggressive Progression in Glioblastoma Cells through Potentiated Activation of Integrin alpha5beta1 by the Tenascin-C-Derived Peptide TNIIIA2, Molecular Cancer Therapeutics, 20190918
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7. Acyclic Retinoid Combined With Tenascin-C-derived Peptide Reduces the Malignant Phenotype of Neuroblastoma Cells Through N-Myc Degradation, Anticancer Research, 2019
   Link to Paper Search Results by DOI
8. TAp63 represses transcription of MYCN/NCYM gene and its high levels of expression are associated with favorable outcome in neuroblastoma, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 518(2), 311-318, 2019
9. Erratum: Combining peptide TNIIIA2 with all-trans retinoic acid accelerates N-Myc protein degradation and neuronal differentiation in MYCN-amplified neuroblastoma cells., American journal of cancer research, 10(1), 2020
10. Involvement of Integrin-Activating Peptides Derived from Tenascin-C in Cancer Aggression and New Anticancer Strategy Using the Fibronectin-Derived Integrin-Inactivating Peptide., Molecules (Basel, Switzerland), 25(14), 2020
11. Exposure of the cryptic de-adhesive site FNIII14 in fibronectin molecule and its binding to membrane-type eEF1A induce migration and invasion of cancer cells via β1-integrin inactivation., American journal of cancer research, 10(11), 2020
12. Induction of cellular senescence in fibroblasts through beta1-integrin activation by tenascin-C-derived peptide and its protumor effect, American Journal of Cancer Research, 11(9), 4364-4379, 20211028
13. Anoikis resistance conferred by tenascin-C-derived peptide TNIIIA2 and its disruption by integrin inactivation, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 536, 14-19, 20210115
    Link to Paper Search Results by DOI
14. A novel method to purify neutrophils enables functional analysis of zebrafish hematopoiesis., Genes to cells : devoted to molecular & cellular mechanisms, 25(12), 2020

Invited Lecture, Oral Presentation, Poster Presentation

1. Combination of all-trans retinoic acid with tenascin-C derived peptide enhances neural differentiation of MYCN-amplified neuroblastoma cells, Manabu Sasada, Kazuki Otsuka, Yoichiro Isohama and Fumio Fukai, Yusuke Suenaga, Sana Yokoi, World Congress on Cancer Science and Therapy, 2019/07/15, Without Invitation, English, Henry Bruce, Rome, Italy, Neuroblastoma is one of the common pediatric tumors. Among the neuroblastoma patients, high-risk group is characterized by amplification of the MYCN gene, which codes N-Myc protein. Excessively expressed N-Myc protein inhibits neuronal differentiation during normal development, which is a central aspect of neuroblastoma genesis. Despite mass-chemotherapy, the survival rate for high-risk neuroblastoma remains extremely low. Besides this low treatment efficacy, mass-chemotherapy has additional severe side effects, so-called “late effects”, that occur many years after chemotherapy has ended. To solve this problem, differentiation therapy using retinoic acid and its derivatives has been expected as a mild chemotherapy with low risk of the late effects. However, the clinical outcome of differentiation therapy using retinoids including all-trans retinoic acid (ATRA) and its derivatives has not been sufficient due to the differentiation inhibition by over-expressed N-Myc protein. In the present study, we succeeded in synergistically accelerating the ATRA-induced neural differentiation of MYCN-amplified neuroblastoma cells by combining a peptide derived from tenascin-C, termed TNIIIA2, which has a potent ability to activate β1-integrins. Achievement of the high efficacy of neural differentiation was attributed to the induction of proteasome degradation of N-Myc protein by the combination of ATRA and TNIIIA2. Importantly, this enhanced differentiation was accompanied by a marked reduction of the malignant phenotype of neuroblastoma cells, and an in vivo experiment showed therapeutic potential of the combination therapy. These results provide a new insight into differentiation therapy for high-risk neuroblastoma based on N-Myc protein degradation.